Viscosity of Near-Boiling NonAssociated Liquids: Dependence on Surface Tension,Molecular Mass and IntraMolecular Conformational Transitions

The equation proposed for near-boiling nonassociated liquids describes a new functional dependence of their viscosity on such physico-chemical characteristics as surface tension and molecular mass. It is shown that the viscosity of liquids with conformationally flexible molecules can be calculated adequately by taking into account the influence of intramolecular conformational transitions on the number of bimolecular collisions in the liquid phase.     

Molecular dynamics simulations of a nucleoside analogue of 1,4-dihydro-4-oxoquinoline-3-carboxylic acid synthesized as a potential antiviral agent: Conformational studies in vacuum and in water

Conformational analysis of nucleosides may have direct applications to the structure–activity relationship (SAR) studies and in the design of new drug candidates. Although conformational analysis may be accessed in many different ways, in this work it was performed using molecular dynamics (MD) simulation in order to study the dynamic behavior of a nucleoside derivative of 1,4-dihydro-4-oxoquinoline-3-carboxylic acid, synthesized by our group as a potential antiviral agent. The MD simulation was carried out during 10 ns in vacuum and in a box of water at two different temperatures (i.e., 300 and 600 K) using the AMBER force field. The in vacuum MD simulation results are in agreement with the crystallographic structure and with the DFT calculations of the nucleoside, revealing the anti conformer as the more stable one. The simulation in water, however, shows that both conformers may exist at 300 K, the temperature of the in vivo and in vitro assays, revealing that both the syn and anti conformers should be considered in a MD simulation study of the inhibitor–enzyme complex. Simulations are also in agreement with the NOE experiment, which shows that the anti conformer is the preferential one in DMSO-d6 solution at 298 K.     

Conformational analysis. Part 16 Conformational free energies in substituted piperidines and piperidinium salts

Summary The conformational free energies (-G^o) of a number of 4-substituted piperidines and piperidinium salts have been determined by the J-value method. For the 4-substituted piperidines (R=Me, Phenyl, CO₂Et, Br, OH, F) the relative conformer energies are almost identical to those of the analogous cyclohexanes.The methyl and phenyl compounds showed no change in the couplings on protonation, implying no change in the conformer energies. In constrast, in the remaining compounds with polar 4-substituents an almost constant stabilisation of the axial conformer of ca. 0.7–0.8 kcal mol^-1 was observed on protonation. In three cases (R=F, OH and Br) the conformational preferences is reversed on protonation and the axial form is favoured.The conformer energies of both the free bases and the piperidinium salts can be quantitatively predicted by molecular mechanics calculations using the COSMIC force-field, in which the electrostatic interactions are calculated by a simple Coulombic model with the partial atomic charges in the molecules given by the CHARGE2 routine, and an effective dielectric constant of five. The precise agreement obtained demonstrates conclusively that the electrostatic interactions between the substituents and the protonated nitrogen are the cause of the conformational changes on protonation, and that these can be modelled successfully using existing force-fields.For Part 15, see Ref. 1.     

Synthesis of a New pH-Dependent Ligand: Conformational and Complexation Studies

A new macrocyclic ligand, 3, which exhibits pH-induced conformational changes, has been prepared. This ligand consists of a crown ether derived from a trans-anti-trans 1,2,4,5-tetrasubstituted cyclohexane. Due to the stereochemistry of the substituents on the carbocyclic ring, two different low-energy conformations of the crown ether are possible. Ligand 3 has been studied in solution by ¹H NMR spectroscopy at different values of pH and temperature, showing that the conformation of the crown ether, and thus its complexing ability, is strongly pH-dependent. The solid-state structure of the ligand has been determined by X-ray diffraction.     

Promoter-Controlled Synthesis and Conformational Analysis of Cyclic Mannosides up to a 32-mer

Cyclodextrins are widely used as carriers of small molecules for drug delivery owing to their remarkable host properties and excellent biocompatibility. However, cyclic oligosaccharides with different sizes and shapes are limited. Cycloglycosylation of ultra-large bifunctional saccharide precursors is challenging due to the constrained conformational spaces. Herein we report a promoter-controlled cycloglycosylation approach for the synthesis of cyclic α-(1→6)-linked mannosides up to a 32-mer. Cycloglycosylation of the bifunctional thioglycosides and (Z)-ynenoates was found to be highly dependent on the promoters. In particular, a sufficient amount of a gold(I) complex played a key role in the proper preorganization of the ultra-large cyclic transition state, providing a cyclic 32-mer polymannoside, which represents the largest synthetic cyclic polysaccharide to date. NMR experiments and a computational study revealed that the cyclic 2-mer, 4-mer, 8-mer, 16-mer, and 32-mer mannosides adopted different conformational states and shapes.     

A Conformational Study on Silacyclohexane. Comparison of ab initio (HF,MP2), DFT,and Molecular Mechanics Calculations. Conformational Energy Surface of Silacyclohexane

The structures and relative energies for the basic conformations of silacyclohexane 1 have been calculated using HF, RI‐MP2, RI‐DFT and MM3 methods. All methods predict the chair form to be the dominant conformation and all of them predict structures which are in good agreement with experimental data. The conformational energy surface of 1 has been calculated using MM3. It is found that there are two symmetric lowest energy pathways for the chair‐to‐chair inversion. Each of them consists of two sofa‐like transition states, two twist forms with C₁ symmetry (twist‐C₁), two boat forms with Si in a gunnel position (C₁ symmetry), and one twist form with C₂ symmetry (twist‐C₂). All methods calculate the relative energy to increase in the order chair < twist‐C₂ < twist‐C₁ < boat. At the MP2 level of theory and using TZVP and TZVPP (Si atoms) basis sets the relative energies are calculated to be 3.76, 4.80, and 5.47 kcal mol^–1 for the twist‐C₂, twist‐C₁, and boat conformations, respectively. The energy barrier from the chair to the twisted conformations of 1 is found to be 6.6 and 5.7 kcal mol^–1 from MM3 and RI‐DFT calculations, respectively. The boat form with Si at the prow (C_s symmetry) does not correspond to a local minimum nor a saddle point on the MM3 energy surface, whereas a RI‐DFT optimization under C_s symmetry constraint resulted in a local minimum. In both cases its energy is above that of the chair‐to‐twist‐C₁ transition state, however, and it is clearly not a part of the chair‐to‐chair inversion.     

新型可用于荧光标记的α-氰基丙烯酸酯单体的合成及在小鼠活体成像中的应用

设计合成了新型含有荧光基团的α-氰基丙烯酸酯单体,并与其它α-氰基丙烯酸酯单体共聚,得到产生荧光的聚氰基丙烯酸酯材料.将其包埋在小鼠背部肌肉层,可获得良好的荧光成像效果.通过对荧光强度的监测,初步研究了聚氰基丙烯酸酯材料中的侧链酯基在小鼠体内的降解情况.单体合成是以蒽合氰基丙烯酸和4,4'-二甲氧基三苯基-氨基己醇为原料,得到蒽合氰基丙烯酸(4,4'-二甲氧基三苯基-氨基己醇)酯,脱保护后再将异硫氰酸荧光素以化学键合的方式标记在末端氨基上,脱蒽还原烯双键后,得到可用于荧光标记的α-氰基丙烯酸(异硫氰酸荧光素-氨基己醇)酯单体.反应中间体及单体结构采用核磁共振氢谱和质谱进行表征.该单体及其高聚物均可在激发光(488 nm)和发射光(525 nm)条件下观察到明显荧光.     

用能量转移探测萘-蒽二元分子体系的构象变化

合成了一个带有末端取代的能量给体-萘和能量受体-蒽的开链冠醚（DSA）.吸收光谱表明两个发色团之间在基态时没有相互作用.选择性激发萘观察到萘的荧光强度下降, 同时伴随着蒽的发射增强, 表明发生了从萘至蒽的单重态-单重态能量转移.能量转移效率受溶剂极性的影响.可以认为在极性小的溶剂如苯中－OCH2CH2O－单元中的中心C－C键主要以反式存在,而在极性大的溶剂如乙腈中则以邻交叉式为主.因此,开链冠醚末端取代的萘和蒽之间的距离随着溶剂极性的增大,能量转移效率却随之降低.表明能量转移可以用于探测以柔性配体键连接的给体-受体体系在不同极性溶剂中的构象变化特性.     

Conformational change in a urea catalyst induced by sodium cation and its effect on enantioselectivity of a Friedel-Crafts reaction

While developing bis-camphorsulfonyl urea as a hydrogen-bonding catalysts, we discovered that the native conformation of the catalyst is unsuitable for inducing enantioselectivity. By complexing the catalyst with weakly Lewis acidic sodium cations, we were able to change the conformation of the catalyst and attain a significant improvement in the selectivity. We provide structural information from X-ray crystallography to show that the uncomplexed catalyst is indeed in an unfavorable conformation. Infrared and Raman spectroscopic studies show that sodium binds the catalyst through the carbonyl and sulfonyl groups. Simulated IR and Raman spectra match well with the experimentally recorded spectra, thereby corroborating the proposed conformational change. This result shows that weak Lewis acids can be used to tune the conformation of hydrogen-bonding catalysts and enhance the selectivity of reaction catalyzed by these systems.     

Conformational and docking studies of acyl homoserine lactones as a robust method to investigate bioactive conformations

A method aiming at investigating possible bioactive conformations of acyl homoserine lactone (AHL) quorum sensing (QS) modulators is established. The method relies on the exhaustive conformational analysis of AHLs by varying torsion angles around the amide group then on the selection of the closest conformation to those known from co-crystallized XRD data of AHL-receptor complexes. These latter are then docked as rigid ligand within the receptor binding site, leading to interactions with binding site residues which are highly consistent as compared with the data arising from XRD studies. The method is first validated using AHLs for which XRD data of their complexes with their cognate receptor are available, then extended to examples for which the binding mode is still unknown.Three compounds were used to validate the method: hexanoyl homoserine lactone (HHL) as an example of autoinducer, 3-oxo-butanoyl homoserine lactone (OBHL), as a representative model of 3-oxo-AHLs, and 4-(4-chlorophenoxy)butanoyl homoserine lactone (CPOBHL) as an example of a QS inhibitor. The conformational analysis of these three compounds to their cognate protein (TraR, SdiA, LasR and CviR) provides the data which enable the next rigid docking step. Further rigid docking of the closest conformations compared to the known bioactive ones within the binding sites allows to recover the expected binding mode with high precision (atomic RMSD < 2 Å). This “conformational analysis/torsion angle filter/rigid ligand docking” method was then used for investigating three non-natural AHL-type QS inhibitors without known co-crystallized XRD structures, namely was 2-hexenoyl homoserine lactone (HenHL), 3-oxo-4-phenylbutanoyl homoserine lactone (OPBHL) and 3-(4-bromophenyl)propanoyl homoserine lactone (BPPHL). Results provide insights into their possible binding mode by identifying specific interactions with some key residues within the receptor binding site, allowing discussion of their biological activity.     

Conformational and stereoelectronic investigation in 1,2-difluoropropane: The gauche effect

The effect of attaching an additional fluorine atom at C-2 in 1-fluoropropane (FP), giving 1,2-difluoropropane (DFP), on its conformational equilibrium, is theoretically evaluated. This substitution causes critical implications on the conformer stabilities of DFP (TG, GT and GG conformations) and the steric and electrostatic interactions should favor the conformer with fluorine atoms trans. However, the gauche effect plays a major role in describing the energies balance in DFP, shifting the equilibrium towards the conformation in which the two fluorine atoms are gauche. The origin of this effect is discussed through an NBO analysis, which allows the evaluation of both classical and non-classical (hyperconjugation and bent bonds) interactions as the prevailing factors governing the conformational equilibrium of molecules containing the 1,2-difluoroethane fragment.     

Fluorogenic N,O-chelates built on a C2-symmetric aryleneethynylene platform: Spectroscopic and structural consequences of conformational preorganization and ligand denticity

Using π-extended aryleneethynylene as a rigid structural skeleton, a C₂-symmetric bis(picolinate) ligand was prepared. Binding of zinc(II) or cadmium(II) ion to this formally tetradentate N₂O₂-chelate resulted in significant red-shifts and enhancement in emission. The metal-ligand interaction responsible for such structural change was investigated by isolation and characterization of a tetrazinc(II) complex, in which the picolinate group functions not only as terminal bidentate but also as bridging with its μ-1,3 carboxylate unit.     

An Ab Initio Study of Conformational Energies in Dioxo-, Trioxo-, and Tetroxo-Dithianes

Ab initio Hartree–Fock calculations at the HF/6-31G* level of theory for geometry optimization and the MP2/6-31G*//HF/6-31G* and B3LYP/6-311G(2df,p)//HF/6-31G* levels for a single point total energy calculation are reported for the important energy-minimum conformations of 1,1-dioxo-thiane (2), 1,1-dioxo-1,2-dithiane (3), 1,1-dioxo-1,3-dithiane (4), 1,1-dioxo-1,4-dithiane (5), 1,1,2-trioxo-1,2-dithiane (6), 1,1,3-trioxo-1,3-dithiane (7), 1,1,4-trioxo-1,4-dithiane (8), 1,1,2,2-tetroxo-1,2-dithiane (9), 1,1,3,3-tetroxo-1,3-dithiane (10), and 1,1,4,4-tetroxo-1,4-dithiane (11). According to the MP2/6-31G*//HF/6-31G* calculations, compound 5 is more stable than 3 and 4 by 7.8 and 8.9 kJ mol^?1, respectively. The axial geometries of 6 and 8 are more stable than the equatorial forms by 21.4 and 19.1 kJ mol^?1, respectively, but the equatorial form of 7 is 4.1 kJ mol^?1 more stable than the axial geometry. Compound 11 is more stable than 9 and 10 by 49.3 and 31.0 kJ mol^?1, respectively.     

以β-二酮连接的含生色团丙烯酰类单体及其饱和模型化合物的荧光行为

通过合成一系列同一分子中既含有给电子性荧光生色团又含缺电子性碳碳双键的烯类单体, 发现这类单体在相同生色团浓度下的荧光强度均明显低于相应的饱和模型化合物或聚合物[1～3]. 这种现象称为荧光结构自猝灭效应(SSQE), 以区别于浓度自猝灭现象. 对于电子状态与之相反的单体, 即含受电子性荧光生色团的乙烯基醚类单体, 也观察到了SSQE[4,5]. 进一步的研究结果表明, SSQE是光照条件下分子内电子给受体之间电荷转移作用的结果, 分子中电子给受体间的间隔基长度和溶剂的性质等都对SSQE有显著的影响[6]. 以往合成的含给生色团的丙烯酰类单体, 其电子给受体间是通过饱和脂肪链相连, 当生色团和受电子性碳碳双键之间以β-二酮结构相连时, 这类单体的荧光性质如何, 是否发生SSQE是我们的关注所在. 另一方面, β-二酮类化合物在一定波长光照射条件下, 常发生烯醇式与酮式的互变异构化. 虽然已有许多文献报道有关烯醇式-酮式互变异构过程中各种光谱的变化以及用核磁、红外、紫外等光谱手段研究烯醇式-酮式互变异构动力学, 但有关β-二酮类化合物互变异构过程中荧光光谱的变化的报道却很少[7～11]. 本文合成了以β-二酮连接的含二甲氨基苯基生色团的烯类单体, 1-(4-二甲氨基苯基)-4-甲基-4-戊烯-1,3-二酮(DMPDK)及其饱和模型化合物1-(4-二甲氨基苯基)-1,3-丁二酮(DMBDK), 研究了其光谱性质及光致互变异构行为.     

多肽抑制剂抑制淀粉质多肽42构象转换的分子动力学模拟和结合自由能计算

应用分子动力学模拟和结合自由能计算方法研究了多肽抑制剂KLVFF、VVIA和LPFFD抑制淀粉质多肽42 (Aβ42)构象转换的分子机理. 结果表明, 三种多肽抑制剂均能够有效抑制Aβ42的二级结构由α-螺旋向β-折叠的构象转换. 另外, 多肽抑制剂降低了Aβ42分子内的疏水相互作用, 减少了多肽分子内远距离的接触, 有效抑制了Aβ42的疏水塌缩, 从而起到稳定其初始构象的作用. 这些抑制剂与Aβ42之间的疏水和静电相互作用(包括氢键)均有利于它们抑制Aβ42的构象转换. 此外, 抑制剂中的带电氨基酸残基可以增强其和Aβ42之间的静电相互作用(包括氢键), 并降低抑制剂之间的聚集, 从而大大增强对Aβ42构象转换的抑制能力. 但脯氨酸的引入会破坏多肽的线性结构, 从而大大降低其与Aβ42 之间的作用力. 上述分子模拟的结果揭示了多肽抑制剂KLVFF、VVIA和LPFFD抑制Aβ42构象转换的分子机理, 对于进一步合理设计Aβ的高效短肽抑制剂具有非常重要的理论指导意义.     

A Simple and Convenient Strategy for the Synthesis of Tolanophanes: Synthesis,Characterization and Conformational Analysis of a Novel Tolanophane

The bromination/dehydrobromination of stilbenophanes as a practical, simple and efficient strategy is applied to the synthesis of tolanophanes 1a (n = 2) and 1b (n = 4). The method is significantly superior to the reported methods. A careful conformational study on a novel tolanophane 1b showed that the relative stability of its conformers is directly linked to both twist angle between the two arene rings and the orientation of the alkoxy groups. The strong interaction between 1b and CDCl₃ at ? 60°C is an unusual feature that is attributed to high restriction in its molecular motion.     

Conformational preferences in methylsilane and disilane. A quantitative non-empirical analysis of the importance of the hyperconjugative interactions

We have investigated the importance of the hyperconjugative interactions in determining the conformational preferences in methylsilane and disilane, and for comparative purposes also in ethane, using a procedure that provides quantitative information about the energy effects associated with orbital interactions. It is found that (1) these interactions are in all cases destabilizing and less destabilizing in the staggered conformation and that (2) in the absence of these interactions, in ethane the staggered conformer is still more stable, while in methylsilane and disilane the eclipsed conformer becomes more stable.We have also investigated the effects of each type of orbital interaction in terms of a quantitative perturbational analysis.     

通过非共价构象锁定和端基工程策略设计高效率的A-D-A型稠环电子受体

近年来,非富勒烯太阳能电池的发展迅猛。目前报道的高效率的非富勒烯稠环电子受体主要采用受体-给体-受体(A-D-A)型结构。本工作中,我们在给受体间引入3,4-二己氧基噻吩作桥,用5,6-二氯-3-(二氰基亚甲基)靛酮作端基设计合成了一种新的稠环电子受体(ITOIC-2Cl)。一方面,可以通过S···O和O···H等作用在分子内形成非共价键构象锁促进分子的平面性;另一方面,通过增加端基的缺电子性可以增强分子内的电荷迁移。在两者的协同作用下,ITOIC-2Cl的光谱吸收拓宽到近红外区,这有利于获得宽的光谱响应。将ITOIC-2Cl与一种吸收互补的给体聚合物(PBDB-T)共混制备活性层,我们用原子力显微镜(AFM)和透射电子显微镜(TEM)表征其形貌,发现共混薄膜可以形成纤维状的互传网络结构和合适纳米尺寸的相分离,这有利于电荷的分离和传输,从而获得高的短路电流(J_(sc))和填充因子(FF)。最终,基于PBDB-T:ITOIC的电池,我们获得了9.37%的光电转换效率,其开路电压(V_(oc))为0.886 V,J_(sc)为17.09 mA·cm~(-2),FF为61.8%。这些研究结果为我们提供了一种设计高效率的非富勒烯稠环电子受体的有效的策略。     

Time evolution of the solvated and conformationally relaxed emissive excited state of the anionic form of salophen,a Schiff base

Salophen is a weakly fluorescent Schiff base which forms emissive co-ordination complexes with Zn²⁺ and Al³⁺. The complex with Al³⁺ is significantly more fluorescent than that with Zn²⁺, presumably because the dimeric complex with Zn²⁺ is associated with additional nonradiative channels. This contention has been put to test, through a careful investigation of excited state dynamics of the anionic form of salophen (Sal²⁻), which is the form in which the ligand exists in the complexes. The emissive excited state of the anion (Sal²⁻) has been found to be solvated and conformationally relaxed, over tens of picosecond. It is significantly more fluorescent than the neutral compound, with fluorescence lifetime that is longer by almost two orders of magnitude. Fluorescence lifetime of the anion is in fact longer than that of the complex with Zn²⁺ and slightly less than that of the complex with Al³⁺. So, the earlier hypothesis about additional nonradiative deactivation pathways in the Zn²⁺ complex gains credence from the present study.